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Acrebol, a novel toxic peptaibol produced by an Acremonium exuviarum indoor isolate
M A Andersson1, R Mikkola, M Raulio
1Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland.
Aims:
To identify a toxin and its producer isolated from woody material in a building where the occupants experienced serious ill health symptoms.
Methods And Results:
Hyphal extracts of an indoor fungus, identified as the cycloheximide-tolerant species Acremonium exuviarum, inhibited motility of boar spermatozoa (EC(50) 5 +/- 2 microg of crude solids ml(-1)) and caused cytolysis of murine neuroblastoma cells (MNA) and feline fetal lung cells (FL). The responsible substances were purified and identified as two structurally similar, heat-stable, novel, toxic peptaibols, 1726 Da and 1740 Da, respectively, with amino acid sequences of Acetyl-Phe-Iva/Val-Gln-Aib-Ile-Thr-Leu-Aib-Pro-Aib-Gln-Pro-Aib-(X-X-X)-SerOH and Acetyl-Phe-Iva/Val-Gln-Aib-Ile-Thr-Leu-Val-Pro-Aib-Gln-Pro-Aib-(X-X-X)-SerOH. Purified acrebol inhibited motility of boar sperm, depleted ATP half-content in 1 day (EC(50) of 0.1 microg ml(-1), 60 nmol l(-1)) depolarised the mitochondria after 2 days, but did not affect the cellular content in NADH. This indicates mitochondrial toxicity. Plate-grown biomass of A. exuviarum BMB4 contained 0.1-1% (w/w) of acrebol, depending on the culture medium.
Conclusions:
Acrebol paralysed the energy generation of mammalian cells suggesting that mitochondria were its target of action.
Significance And Impact Of The Study:
Acremonium exuviarum, as an indoor fungus, is potentially hazardous to health because of the toxic peptaibols that it produces.
Insights
An indoor fungus, Acremonium exuviarum, produces toxic peptaibols called acrebol. This toxin targets mammalian cell mitochondria, paralyzing energy generation and potentially causing illness in building occupants.
Area of Science:
- Mycology
- Toxicology
- Cell Biology
Background:
- Building-associated fungal contamination can lead to occupant ill health.
- Identification of specific fungal toxins is crucial for understanding health impacts.
Purpose of the Study:
- To identify the toxin and its producing organism linked to severe health symptoms in building occupants.
- To characterize the toxicological properties of the identified fungal metabolites.
Main Methods:
- Isolation and identification of a fungus from indoor woody material.
- Extraction and purification of toxic compounds from fungal hyphae.
- Assessment of the effects of purified toxins on boar spermatozoa and mammalian cell lines (murine neuroblastoma and feline fetal lung cells).
- Analysis of the mechanism of toxicity, including effects on cellular ATP and mitochondrial membrane potential.
Main Results:
- Acremonium exuviarum was identified as the causative indoor fungus.
- Two novel, heat-stable toxic peptaibols, termed acrebol (1726 Da and 1740 Da), were isolated and structurally characterized.
- Acrebol inhibited boar sperm motility and caused cytolysis of mammalian cells.
- Acrebol demonstrated mitochondrial toxicity by depleting ATP and depolarizing mitochondria, without affecting cellular NADH levels.
- The fungus produced 0.1-1% acrebol by weight, depending on the culture medium.
Conclusions:
- Acrebol, produced by Acremonium exuviarum, targets the energy generation process in mammalian cells, specifically acting on mitochondria.
- Acremonium exuviarum is identified as a potentially health-hazardous indoor fungus due to its production of toxic peptaibols.
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